Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India.

Background: This post hoc analysis evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) from India.

Methods: Changes from baseline in HbA1c, fasting plasma glucose (FPG), body weight, and blood pressure (BP) with canagliflozin 100 and 300 mg were evaluated in a subgroup of patients from India (n = 124) from 4 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 2313; Population 1). Safety was assessed based on adverse event (AE) reports in these patients and in a broader subgroup of patients from India (n = 1038) from 8 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 9439; Population 2).

Ethnic Variations in Diabetes and Prediabetes Prevalence and the roles of Insulin Resistance and β-cell Function: The CARRS and NHANES Studies.

Aims: It is unclear how the prevalence of diabetes in Asian Indians in urban India compares to that of race/ethnic groups in the US that may have different underlying susceptibilities. Therefore we examined ethnic variations in the prevalence of type 2 diabetes, iIFG, iIGT, IFG+IGT, and the associated risk factors in Asian Indians in Chennai, India, and Whites, Blacks, and Hispanics in the United States.

Methods: Cross-sectional analyses, using representative samples of 4,867 Asian Indians aged 20-74 years from Chennai, India in the Centre for Cardiometabolic Risk Reduction in outh-Asia study (CARRS) (2010-2011) and 6,512 US Whites, Blacks, and Hispanics aged 20-74 years from the National Health and Nutrition Examination Survey (NHANES) (2007-2012).

Slowing the diabetes epidemic in the World Health Organization South-East Asia Region: the role of diet and physical activity.

The nutrition transition occurring in the World Health Organization South-East Asia Region, as a result of rapid urbanization and economic development, has perhaps made this region one of the epicentres of the diabetes epidemic. This review attempts to evaluate the role of diet and physical inactivity in the South-East Asia Region in promoting this epidemic and points to strategies to slow it down by lifestyle modification. The emerging new food-production technologies and supermarkets have made energy-dense foods more easily available.

Does tight control of systemic factors help in the management of diabetic retinopathy?

Diabetic retinopathy (DR), one of the leading causes of preventable blindness, is associated with many systemic factors that contribute to the development and progression of this microvascular complication of diabetes. While the duration of diabetes is the major risk factor for the development of DR, the main modifiable systemic risk factors for development and progression of DR are hyperglycemia, hypertension, and dyslipidemia. This review article looks at the evidence that control of these systemic factors has significant benefits in delaying the onset and progression of DR.

Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.

Background: Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF).

Altered immunometabolism at the interface of increased endoplasmic reticulum (ER) stress in patients with type 2 diabetes.

The mechanism of perturbed immune function in patients with T2DM is poorly understood. Recent studies imply a role for ER stress in linking immune-system alterations and metabolism. Here, we investigated whether ER stress markers and its downstream effector signals are altered in patients with type 2 diabetes along with proinflammatory augmentation.

Diabetes in India: what is different?

Purpose Of Review: The purpose of this study was to review the epidemiology and pathogenesis of diabetes in Asian Indians with a particular focus on 'Asian Indian type 2 diabetes phenotype'.

Recent Findings: The prevalence of diabetes is rapidly increasing among Asian Indians, particularly in the past two decades. The diabetes rates in urban India now exceed that seen in Indians migrated to developed nations.

Impaired toll-like receptor signalling in peripheral B cells from newly diagnosed type-2 diabetic subjects.

Toll-like receptors (TLRs) under diabetic conditions trigger inflammation and impair immunity. In the present study, we looked at the expression of TLRs (2 and 4) and their adaptors in Normal Glucose Tolerant (NGT), Newly Diagnosed Type-2 Diabetic (NDD) and Known Type-2 Diabetic (KDM) subjects. We also estimated TLR induced cytokine secretion, cellular activation and apoptosis.

Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence.

Monocyte dysfunction by filarial antigens has been a major mechanism underlying immune evasion following hyporesponsiveness during patent lymphatic filariasis. Recent studies have initiated a paradigm shift to comprehend the immunological interactions of Wolbachia and its antigens in inflammation, apoptosis, lymphocyte anergy, etc. Here we showed that recombinant Wolbachia heat shock protein 60 (rWmhsp60) interacts with TLR-4 and induces apoptosis in monocytes of endemic normal but not in chronic patients.

Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease.

India is experiencing an alarming rise in the burden of noncommunicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores.

SEAP activity serves for demonstrating ER stress induction by glucolipotoxicity as well as testing ER stress inhibitory potential of therapeutic agents.

Endoplasmic reticulum (ER) stress is emerging as a unifying paradigm and one of the underlying mechanisms in the genesis of diabetes and its complications. While this has prompted the development of ER stress inhibitors, there is a limitation in monitoring of ER stress in vitro and in vivo by reliable methodologies. We validated the secreted alkaline phosphatase (SEAP) activity as a surrogate marker of ER stress in mouse β-TC6 cells exposed to glucolipotoxicity or tunicamycin and studied insulin secretion along with alterations in ER stress markers.

Soluble CD36 in plasma and urine: a plausible prognostic marker for diabetic nephropathy.

Aims: This study was designed to analyze the level of soluble CD36 (sCD36) in both plasma and urine of type 2 diabetic patients with and without microalbuminuria/macroalbuminuria.

Methods: Study subjects (n=20 each) comprised of those with normal glucose tolerance, type 2 diabetes (T2DM) with normoalbuminiria, T2DM with microalbuminuria and T2DM with macroalbuminuria. The biochemical parameters were analyzed using auto-analyzer, and the level of sCD36 was estimated using an in-house Sandwich ELISA.

Serum IL-9, IL-17, and TGF-β levels in subjects with diabetic kidney disease (CURES-134).

The role of inflammation in both diabetes and diabetic kidney disease (DKD) is becoming more widely accepted. However, the role of recently characterized T cell cytokines interleukin (IL)-9 and IL-17 in diabetes and especially DKD is less well studied. Transforming growth factor beta (TGF-β) controls the secretion of both of these cytokines.

Comparison of relative waist circumference between Asian Indian and US adults.

Background: Relative to Europeans, Asian Indians have higher rates of type 2 diabetes and cardiovascular disease. Whether differences in body composition may underlie these population differences remains unclear.

Methods: We compared directly measured anthropometric data from the Chennai Urban Rural Epidemiology Study (CURES) survey of southern Indians (I) with those from three US ethnic groups (C: Caucasians, A: African Americans, and M: Mexican Americans) from NHANES III (Third National Health and Nutrition Examination Survey).

Impaired glucose tolerance alters functional ability of peripheral blood-derived mononuclear cells in Asian Indian men.

Aim: To compare the adhesion, migration and endothelial differentiation potential of peripheral blood-derived mononuclear cells (PBMCs) obtained from drug-naive normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) Asian Indian men.

Methods: Based on the 75-g oral glucose tolerance test, 30 NGT and 31 IGT subjects were recruited into the study. PBMCs were isolated from fasting blood using histopaque density gradient centrifugation.

Prevalence of overweight and obesity among school children and adolescents in Chennai.

Objective: To determine the prevalence of overweight and obesity among children and adolescents in Chennai, India, using national and international age- and sex- specific body mass index (BMI) cut-off points.

Methods: The Obesity Reduction and Awareness and Screening of Non communicable diseases through Group Education in Children and Adolescents (ORANGE) project is a cross-sectional study carried out on 18,955 children (age 6-11 years) and adolescents (age 12-17 years) across 51 schools (31 private and 20 government) of Chennai. Overweight and obesity was classified by the International Obesity Task Force (IOTF 2000) and Khadilkars criteria (2012), and Hypertension by the IDF criteria (in children ≥10 years and adolescents).

Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study.

Objectives: DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India.

Materials And Methods: This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit.

Tele-diabetology to Screen for Diabetes and Associated Complications in Rural India: The Chunampet Rural Diabetes Prevention Project Model.

Diabetes, with its acute and long-term complications, has become a major health hazard in developing countries. An estimated 62.4 million people in India have diabetes.

Human islet mass, morphology, and survival after cryopreservation using the Edmonton protocol.

The aim of this study was to assess recovery, cell death, and cell composition of post-thaw cultured human islets. Cryopreserved islets were provided by the Clinical Islet Transplant Program, Edmonton, Canada. Islets were processed using media prepared in accordance with Pre-Edmonton and Edmonton protocols.

Why are clinical trials necessary in India?

Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants.

Benefits of early glycemic control by insulin on sensory neuropathy and cataract in diabetic rats.

While there is an emphasis on the early glycemic control for its long-term benefits in preventing microvascular complications of diabetes, the biochemical mechanisms responsible for the long-lasting effects are not clearly understood. Therefore the impact of early insulin (EI) versus late insulin (LI) treatment on diabetic sensory neuropathy and cataract in streptozotocin-induced diabetic Wistar male rats were evaluated. EI group received insulin (2.

Hypoglycemia in type 2 diabetes: Standpoint of an experts' committee (India hypoglycemia study group).

The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority. Despite compelling evidence that tight glycemic control is crucial for delaying disease progression, increased risk of hypoglycemia associated with such control underscore the complexity of diabetes management. In most cases, hypoglycemia results from an excess of insulin, either absolute or relative to the available glucose substrate and the factors perhaps exacerbating the risk are pharmacokinetic imperfections, behavioral, co-morbidities etc.

Increased levels of serum granulocyte-macrophage colony-stimulating factor is associated with activated peripheral dendritic cells in type 2 diabetes subjects (CURES-99).

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine with growth factor-like properties for monocytes and dendritic cells (DCs). In the present study, serum GM-CSF levels and the activation status of DCs were studied in type 2 diabetes mellitus (T2DM) subjects.

Methods: Study subjects were recruited from the Chennai Urban Rural Epidemiology Study.

Nutritional and sensory profile of two Indian rice varieties with different degrees of polishing.

Traditional hand-pounded rice has been replaced today with highly polished white rice in the Asian Indian diets. The study aimed to evaluate the nutritional as well as the sensory differences between the brown (0% polish) and the rice milled to different degrees of polish (2.3, 4.